Age prediction using fundus parameters of normal eyes from the Kumejima population study.

PURPOSE: Artificial intelligence can predict the age of an individual using color fundus photographs (CFPs). This study aimed to investigate the accuracy of age prediction in the Kumejima study using fundus parameters and to clarify age-related changes in the fundus. METHODS: We used nonmydriatic CFPs obtained from the Kumejima population study, including 1,646 right eyes of healthy participants with reliable fundus parameter measurements. The tessellation fundus index was calculated as R/(R + G + B) using the mean value of the red-green-blue intensity in eight locations around the optic disc and foveal region. The optic disc ovality ratio, papillomacular angle, and retinal vessel angle were quantified as previously described. Least absolute shrinkage and selection operator regression with leave-one-out cross-validation was used to predict age. The relationship between the actual and predicted ages was investigated using Pearson's correlation coefficient. RESULTS: The mean age of included participants (834 males and 812 females) was 53.4 ± 10.1 years. The mean predicted age based on fundus parameters was 53.4 ± 8.9 years, with a mean absolute error of 3.64 years, and the correlation coefficient between actual and predicted age was 0.88 (p < 0.001). Older patients had greater red and green intensities and weaker blue intensities in the peripapillary area (p < 0.001). CONCLUSIONS: Age could be predicted using the CFP parameters, and there were notable age-related changes in the peripapillary color intensity. The age-related changes in the fundus may aid the understanding of the mechanism of fundus diseases such as age-related macular degeneration.

Interaction of impaired myocardial flow reserve and extent of myocardial ischemia assessed using 13N-ammonia positron emission tomography imaging on adverse cardiovascular outcomes.

BACKGROUND: Myocardial flow reserve (MFR) and the extent of myocardial ischemia identify patients at high risk of major adverse cardiovascular events (MACEs). Associations between positron emission tomography (PET)-assessed extent of ischemia, MFR, and MACEs is unclear. METHOD: Overall, 640 consecutive patients with suspected or known coronary artery disease undergoing 13N-ammonia myocardial perfusion PET were followed-up for MACEs. Patients were categorized into three groups based on myocardial ischemia severity: Group I (n = 335), minimal (myocardial ischemia < 5%); Group II (n = 150), mild (5-10%); and Group III (n = 155), moderate-to-severe (> 10%). RESULTS: Cardiovascular death and MACEs occurred in 17 (3%) and 93 (15%) patients, respectively. Following statistical adjustment for confounding factors, impaired MFR (global MFR < 2.0) was revealed as an independent predictor of MACEs in Groups I (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.48-5.64; P = 0.002) and II (HR, 3.40; 95% CI 1.37-8.41; P = 0.008) but was not significant in Group III (HR, 1.15; 95% CI 0.59-2.26; P = 0.67), with a significant interaction (P < 0.0001) between the extent of myocardial ischemia and MFR. CONCLUSION: Impaired MFR was significantly associated with increased risk of MACEs in patients with ≤ 10% myocardial ischemia but not with those having > 10% ischemia, allowing a clinically effective risk stratification.

Sex determination using color fundus parameters in older adults of Kumejima population study.

PURPOSE: Deep learning artificial intelligence can determine the sex using only fundus photographs. However, the factors used by deep learning to determine the sex are not visible. Therefore, the purpose of the study was to determine whether the sex of an older individual can be determined by regression analysis of their color fundus photographs (CFPs). METHODS: Forty-two parameters were analyzed by regression analysis using 1653 CFPs of normal subjects in the Kumajima study. The parameters included the mean values of red, green, and blue intensities; the tessellation fundus index; the optic disc ovality ratio; the papillomacular angle; and the retinal vessel angles. Finally, the L2 regularized binomial logistic regression was used to predict the sex using all the parameters, and the diagnostic ability was assessed through the leave-one-cross-validation. RESULTS: The mean age of the 838 men and 815 women were 52.8 and 54.0 years, respectively. The ovality ratio and retinal artery angles in women were significantly smaller than that in men. The green intensity at all locations for the women were significantly higher than that of men (P < 0.001). The discrimination accuracy rate assessed by the area-under-the-curve was 80.4%. CONCLUSIONS: Our methods can determine the sex from the CFPs of the adult with an accuracy of 80.4%. The ovality ratio, retinal vessel angles, tessellation, and the green intensities of the fundus are important factors to identify the sex in individuals over 40 years old.

OCULAR FACTORS RELATED TO PREOPERATIVE ENLARGEMENT OF IDIOPATHIC MACULAR HOLE DIAMETER.

PURPOSE: To determine the preoperative factors that are significantly correlated with an enlargement of an idiopathic macular hole (MH) during the one-month preoperative period. METHODS: This was a retrospective cross-sectional study of patients with MH who had undergone vitrectomy in the Kagoshima University Hospital. The stage of the MH was determined by using spectral domain optical coherence tomography. Patients who had optical coherence tomography images at two time points more than 14 days apart before the vitrectomy were studied. RESULTS: The MH participants were at Stage 2 in 44 eyes, at Stage 3 in 58 eyes, and at Stage 4 in 38 eyes. The rate of increase of the hole diameter was 26.0 ± 42.3% at Stage 2, 5.52 ± 15.5% at Stage 3, and 8.04 ± 18.7% at Stage 4. The rate of change at Stage 2 was significantly greater than that at Stage 3 and Stage 4 (both P < 0.01). In Stage 2, the MH diameter at the initial visit was significantly and negatively correlated with the rate of MH enlargement (r = -0.35, P = 0.021). CONCLUSION: Patients with Stage 2 MHs, especially eyes with small hole diameter, should be considered for early surgery.

Relationship between peripapillary choroidal thickness and degree of tessellation in young healthy eyes.

PURPOSE: To determine the relationship between the peripapillary choroidal thickness (ppCT) and the degree and distribution of the tessellation in the fundus of normal eyes. METHODS: This was a prospective, observational cross-sectional study of 118 right eyes of young healthy volunteers. The ppCT was measured from the optical coherence tomography (OCT) circle scans manually at eight sectors: the nasal, supranasal superior, supratemporal, temporal, infratemporal, inferior, and infranasal sectors. The subjective degree of the tessellation in the color fundus photographs (CFPs) was classified into three categories: non-tessellated (NT), weakly tessellated (WT), and strongly tessellated (ST) in same sectors. The objective degree of tessellation designated by the tessellation fundus index (TFI) which was calculated as TFI = (R - G)/(R + G + B) using the mean value of the red-green-blue intensities of the CFPs. The differences in the ppCT and TFI for the three tessellation groups were analyzed. The correlations between the TFI and the ppCT were also determined. RESULTS: The mean age of the subjects was 25.8 years and the mean axial length of the eye was 25.5 mm. The inter-rater agreement of the subjective classifications was high with a Fleiss kappa of 0.71. The ppCT was significantly thinner in eyes with higher degrees of tessellation (P < 0.05) in all sectors. The TFIs were significantly and negatively correlated with the ppCTs in all sectors (r = - 0.44 to - 0.24, P < 0.05) except the nasal and the supranasal sectors. CONCLUSION: The degree of peripapillary tessellation is significantly correlated with the ppCT in young healthy eyes, and it has large individual and geographic variations.

Sex judgment using color fundus parameters in elementary school students.

PURPOSES: Recently, artificial intelligence has been used to determine sex using fundus photographs alone. We had earlier reported that sex can be distinguished using known factors obtained from color fundus photography (CFP) in adult eyes. However, it is not clear when the sex difference in fundus parameters begins. Therefore, we conducted this study to investigate sex determination based on fundus parameters using binominal logistic regression in elementary school students. METHODS: This prospective observational cross-sectional study was conducted on 119 right eyes of elementary school students (aged 8 or 9 years, 59 boys and 60 girls). Through CFP, the tessellation fundus index was calculated as R/(R + G + B) using the mean value of red-green-blue intensity in the eight locations around the optic disc. Optic disc ovality ratio, papillomacular angle, retinal artery trajectory, and retinal vessel were quantified based on our earlier reports. Regularized binomial logistic regression was applied to these variables to select the decisive factors. Furthermore, its discriminative performance was evaluated using the leave-one-out cross-validation method. Sex difference in the parameters was assessed using the Mann-Whitney U test. RESULTS: The optimal model yielded by the Ridge binomial logistic regression suggested that the ovality ratio of girls was significantly smaller, whereas their nasal green and blue intensities were significantly higher, than those of boys. Using this approach, the area under the receiver-operating characteristic curve was 63.2%. CONCLUSIONS: Although sex can be distinguished using CFP even in elementary school students, the discrimination accuracy was relatively low. Some sex difference in the ocular fundus may begin after the age of 10 years.

Association between J-CTO score and long-term target lesion revascularization rate after successful chronic total coronary occlusion angioplasty (from the J-CTO Registry).

OBJECTIVES: The aim of this study was to evaluate the impact of the J-CTO score on long-term target lesion revascularization (TLR) after successful native chronic total occlusion (CTO)-percutaneous coronary intervention (PCI). BACKGROUND: We previously reported that the J-CTO score could be used to stratify the lesion complexity and procedural success rate in CTO lesions. METHODS: We evaluated the prognostic significance of a high J-CTO score for long-term TLR rate in the J-CTO Registry. RESULTS: In the 425 lesions of 408 patients who underwent successful CTO-PCI during a median follow-up of 63.0 (interquartile range: 21.2-72.9) months in the J-CTO Registry, the cumulative incidence of TLR of lesions with a J-CTO score ≥ 2 (n = 216) was significantly higher than in those with a J-CTO score ≤ 1 (n = 209) (27.0 versus 19.4% at 5 years, respectively, P = 0.04). Among 323 lesions of 309 patients with a complete 5-year follow-up, the rate of TLR was 28% (n = 91). A J-CTO score ≥ 2 was independently associated with a higher risk of TLR (odds ratio, 1.73; 95% confidence interval, 1.01-2.99, P = 0.048) even after adjustment for clinically relevant baseline factors. CONCLUSIONS: Patients with high J-CTO score lesions had a higher 5-year risk of TLR.

Differences of body height, axial length, and refractive error at different ages in Kumejima study.

PURPOSE: To determine the relationships between the axial length (AL), refractive error (RE), and body height (BH) at different ages of a genetically-stable population in Kumejima, Japan. METHODS: Cross-sectional, population-based study. Residents of Kumejima who were ≥ 40-years old were studied. The eligible residents had a thorough ocular examinations including measurements of the AL, RE, and BH. The subjects were divided into decade groups. The relationships between the AL, the RE, and the BH of the different decades were determined. RESULTS: Reliable measurements of the AL of the right eyes were obtained from 2198 (1103 men and 1095 women) normal subjects. There was a significant and negative correlation between the age and the BH (r = -0.44, P < 0.001) and the AL (r = -0.27, P < 0.001). There were significant and positive correlations between the BH and AL in all subjects (r = 0.38, P < 0.001). There was a significant and positive correlation between the BH and the AL in all age brackets (r = 0.26~0.49, P < 0.001). There was a significant and positive correlation between the age and RE (spherical equivalent; r = 0.49, P < 0.001). There were significant and negative correlations between the BH and RE in all subjects (r = -0.29, P < 0.001). CONCLUSIONS: The younger individuals tend to be taller, have longer AL, and are more myopic. Considering the marked improvement of the nutritional status during the growth period of each generation and its close association with BH, nutrition may be one of factors that is related to the increase in the prevalence of myopia in the younger generation.

Ability of MultiColor scanning laser ophthalmoscope to detect non-glaucomatous retinal nerve fiber layer defects in eyes with retinal diseases.

PURPOSE: To compare the ability of ocular fundus images obtained by Spectralis MultiColor scanning laser ophthalmoscope (MC-SLO) to that obtained by conventional color fundus images (CF) in detecting non-glaucomatous nerve fiber layer defects (NFLDs). METHODS: A cross-sectional, retrospective study. Patients with retinal diseases who had ocular examination with both the MC-SLO and CF instruments at the Kagoshima University from December 2016 to February 2017 were studied. Eyes that had NFLDs with non-glaucomatous optic discs were analyzed. The visibility of the NFLDs was classified into three grades: grade 0, not visible; grade 1, barely visible; and grade 2, clearly visible. The NFLD grade for blue, green, and red scanning lights of the MC-SLO, merged images with three wavelengths and the color and red-free images were determined by two ophthalmologists. These scores were compared by Steel-Dwass tests. RESULTS: Thirty-one eyes of 26 patients with a mean age of 63.1 ± 11.2 years were studied. There were 14 eyes with diabetic retinopathy, 11 eyes with age-related macular degeneration, 3 eyes with a branch retinal vein occlusion, and 3 eyes with an epiretinal membrane/macular hole. Both the intra-rater (0.631-0.790) and inter-rater (0.637-0.733) agreements were good. NFLDs were detected by the blue wavelength in all cases and by green wavelength and merged wavelengths in 90.3% of the images. The mean NFLD grade was 1.58 ± 0.49 for blue light images, 1.13 ± 0.54 for green light images, 0.07 ± 0.24 for red light images, and 1.16 ± 0.56 for merged images. The NFLD score for blue wavelength was significantly higher than that for green and red wavelength images (P < 0.05 and P < 0.01) but not significantly higher than that for the merged images. NFLDs were detected in 12 eyes (38.7%) in the color images and 16 eyes (51.6%) in the red-free images. The NFLD score for the CF and the red-free image was 0.41 ± 0.55 and 0.70 ± 0.67 which is significantly lower than that of blue MC-SLO images. CONCLUSION: The images obtained by MC-SLO are superior to that obtained by CF in detecting NFLDs in eyes with retinal diseases. We recommend MC-SLO imaging to screen for NFLDs in eyes with retinal diseases.

Effect of fluid-air exchange on reducing residual silicone oil after silicone oil removal.

PURPOSE: Our purpose was to determine the effect of fluid-air exchange on the amount of silicone oil (SO) droplets remaining in the vitreous cavity after removal of the main body of the SO. METHODS: This was a retrospective comparative study of 56 eyes of 56 patients that had undergone vitrectomy with SO tamponade. Fluid-air exchange was performed during surgery in 30 eyes [Air Ex(+) group] and was not done in 26 eyes [Air Ex(-) group]. All of the eyes were examined by ultrasonography, and the images were converted to binarized image. The amount of residual SO droplets/vitreal area in the images was expressed as the, "silicone oil index (SOI)". The correlations between SOI and clinical findings were determined. RESULTS: The SOI was significantly correlated with the axial length (AL, R = 0.444, P = 0.023). The SOI in the Air Ex(+) group was significantly higher (7.4 ± 2.6%) than in the Air Ex(-) group (4.9 ± 3.4%; P = 0.004). Multiple linear regression analyses showed that the SOI was independently and significantly correlated with the AL and the Air Ex(+) group (P = 0.003, P = 0.006, respectively). CONCLUSIONS: Fluid-air exchange during vitrectomy to remove residual SO is not effective. Our findings indicate that it may increase the amount of residual SO droplets.

Association of lifestyle and body structure to ocular axial length in Japanese elementary school children.

BACKGROUND: The purpose of this study is to determine whether the lifestyle and body stature are significantly associated with the axial length (AL) of the eyes of Japanese third grade students. METHODS: A prospective, cross sectional, observational study was performed on 122 third grade students consisting of 61 boys and 61 girls ages 8 to 9 years. The AL, body height, body weight, and body mass index (BMI) were measured. The lifestyle was determined by activities such as the daily duration of indoor studying, television viewing, use of computers and smart phones, outdoor activity time, bed time, Japanese or Western dietary habits, and parental myopia were investigated by a questionnaire with three or five grade levels. The relationship between AL and the questionnaire variables were analyzed by Spearman's correlation analyses. RESULTS: Westernized dietary habits (r = -0.24, P = 0.01), duration of computer and smart phone use (r = 0.24, P = 0.008), parental myopia (r = 0.39, P < 0.001), body weight (r = 0.26, P = 0.005), and BMI (r = 0.23, P = 0.011) were significantly correlated with the AL. Multiple logistic regression analyses showed that the sex [r = -0.48; 95% confidence interval (CI) -0.80 to -0.17, P = 0.003], body weight (r = 0.04; 95% CI 0.02 to 0.07, P = 0.038), westernized dietary habits (r = -0.30; 95% CI -0.55 to -0.05, P = 0.021), and parental myopia (r = 0.40; 95% CI 0.20 to 0.61, P < 0.001) were significantly and independently correlated with the AL. CONCLUSIONS: The body weight and parental myopia and westernized dietary habits are factors significantly associated with myopia. Changing from Japanese food style to westernized food style might increase the risk of progression of school myopia.

Relative changes in luminal and stromal areas of choroid determined by binarization of EDI-OCT images in eyes with Vogt-Koyanagi-Harada disease after treatment.

PURPOSE: The aim of this study was to determine the changes in the luminal and stromal areas of the choroid in eyes with Vogt-Koyanagi-Harada disease by optical coherence tomography (OCT). METHODS: A retrospective observational study. Choroidal images were recorded by enhanced depth imaging (EDI-OCT) at the baseline, and at 1 week and 1 month after initiating steroid therapy. The EDI-OCT images were converted to binarized images, and the luminal areas and the stromal areas were measured separately. RESULTS: Thirty-two eyes of 16 patients were enrolled, and 16 eyes of 10 patients had suitable images for the binarization analyses. The ratio of the luminal areas to the choroidal areas was 0.60 ± 0.03 at the baseline, 0.67 ± 0.04 at 1 week, and 0.66 ± 0.04 at 1 month. There was a significant increase from the baseline at 1 week (P < 0.01) but not from 1 week to 1 month. Although both the stromal and luminal areas were reduced, the percent reduction of the stromal areas (56.5 ± 7.2 %) was significantly greater than that of the luminal areas (42.5 ± 12.6 %) at 1 week (P < 0.01). CONCLUSIONS: A significant decrease of the choroidal area was detected in eyes with Vogt-Koyanagi-Harada disease at 1 week after beginning steroid therapy. The decrease was more evident in the stromal area than in the luminal area.

Clinical outcome of renal artery stenting for hypertension and chronic kidney disease up to 12 months in the J-RAS Study ­ prospective, single-arm, multicenter clinical study.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) causes renovascular hypertension (HTN) and impairs renal function, leading to chronic kidney disease (CKD). The J-RAS study was a prospective, multicenter study to assess the clinical outcome of renal artery stenting for up to 1 year in Japanese patients with ARAS. METHODS AND RESULTS: One hundred and forty-nine patients were enrolled between November 2010 and January 2013. The patients were classified into an HTN (n=121) group and a CKD (n=108) group in the primary analysis. The primary efficacy endpoints were change in blood pressure for the HTN group and change in estimated glomerular filtration rate (eGFR) for the CKD group at 1 months. The primary safety endpoint was freedom from major cardiovascular or renal events at 12 months. In the HTN group, the mean systolic blood pressure (SBP) significantly decreased from 161.6 ± 21 mmHg at baseline to 137.0 ± 21 mmHg (P<0.0001). In the CKD group, there was no significant difference in eGFR from 40.7 ± 10 ml·min(-1)·1.73 m(-2)at baseline to 40.8 ± 13 ml·min(-1)·1.73 m(-2)(P=0.32). The primary safety endpoint was 89.4% at 12 months. CONCLUSIONS: In the J-RAS trial, significant SBP reduction was seen in the HTN group, and stabilization of renal function in the CKD group. Renal artery stenting for ARAS is safe and effective in Japanese patients.

Brilliant Blue G double staining enhances successful internal limiting membrane peeling with minimal adverse effect by low cellular permeability into live cells.

PURPOSE: Brilliant Blue G is used as a surgical adjuvant for retinal surgery. Although BBG double or multiple staining was reported, the effectiveness and safety of repeated staining is still elusive. To further examine the effectiveness and safety, we examined BBG in clinical cases in vivo, primary cell culture in vitro, and surgically resected specimen ex vivo. METHODS: A retrospective interventional case series with in vitro and ex vivo studies were performed. Vitrectomy was performed in 28 cases of epiretinal membrane with BBG single to multiple staining. The surgically resected membranes were stained by BBG with or without cellular fixation. Primary cell cultures were examined with BBG and live/death cell markers, such as Calcein AM and TUNEL. RESULTS: Single staining provided satisfactory staining in seven cases. Double or multiple staining substantially visualized internal limiting membrane (21 cases), especially the edges of remaining internal limiting membrane (11 cases). Adverse retinal staining was not noted and the final visual acuity showed no difference with multiple staining. The live cells barely stained with BBG, while some dead cells were stained. CONCLUSION: Brilliant Blue G multiple staining substantially enhanced the visualization of internal limiting membrane. The absence of abnormal staining supports the safety of repeated BBG staining.

Retinal morphologic changes and concentrations of cytokines in eyes with diabetic macular edema.

PURPOSE: To determine the relationship between the retinal morphologic changes and concentrations of intravitreal cytokines in eyes with diabetic macular edema. METHODS: A retrospective comparative study was performed. The preoperative optical coherence tomography images were evaluated to determine the presence of serous retinal detachments (SRDs), retinal cystic changes, and retinal swelling. The concentrations of vascular endothelial growth factor, interleukin (IL)-6, and IL-8 in vitreous samples collected during vitrectomy were determined. The correlations between optical coherence tomography parameters, other clinical factors, and the concentration of cytokines were calculated. RESULTS: Fifty-two eyes (52 patients) were investigated. An SRD was found in 19 of the 52 eyes (36.5%). Multivariate regression analysis showed that IL-6 was the only factor significantly associated with the presence of an SRD (P = 0.001; odds ratio, 1.268; 95% confidence interval, 1.105-1.452). The other morphologic changes, such as retinal cystic changes and retinal swellings, were not significantly associated with the concentrations of intravitreal cytokines. CONCLUSION: The significant association of SRD with intravitreal IL-6 indicates that inflammation may play an important role in the development of SRD in diabetic macular edema.

Individualized, spectral domain-optical coherence tomography-guided facedown posturing after macular hole surgery: minimizing treatment burden and maximizing outcome.

PURPOSE: To evaluate the individualized, optical coherence tomography-guided facedown posturing after macular hole (MH) surgery in minimizing the burden and maximizing outcome. METHODS: A retrospective comparative study. One hundred and seven consecutive eyes with an MH (<500 µm) received vitrectomy and gas tamponade. After surgery, optical coherence tomography examination was performed from 6 hours to postoperative Day 2. In Group A, with a pro re nata posturing protocol, the duration of facedown posturing was determined from the optical coherence tomography findings. Group A was subdivided as follows: Group A1, facedown posturing required postoperatively and Group A2, no posturing required. When MH closure was confirmed, facedown posturing (if any) was discontinued. If the MH did not close, additional posturing was advised. Group B was the control group, consisted of 42 consecutive eyes with traditional 7 days of posturing. RESULTS: After a single surgery, Group A had the MH closure rate of 96.2%, 95.8% in Group A1 and 97.1% in Group A2, whereas Group B had the MH closure rate of 95.2%. The average posturing period was 42 hours for Group A, 57 hours for Group A1 and 10 hours for Group A2 (P < 0.001). The MH size was correlated significantly with the closure time (R = 0.47, P = 0.005, Spearman correlation coefficient). CONCLUSION: A pro re nata posturing protocol achieves a high MH closure rate with a significant reduction of posturing time especially for pseudophakic eyes.